Background : Patients with chronic infection with hepatitis C virus (HCV) genotype 1 often need 48 weeks of peginterferon-ribavirin treatment for a sustained virologic response. We designed a noninferiority trial (noninferiority margin, -10.5%) to compare rates of sustained virologic response among patients receiving two treatment durations.
Methods : We enrolled patients with chronic infection with HCV genotype 1 who had not previously received treatment. All patients received telaprevir at a dose of 750 mg every 8 hours, peginterferon alfa-2a at a dose of 180 mu g per week, and ribavirin at a dose of 1000 to 1200 mg per day, for 12 weeks (T12PR12), followed by peginterferon-ribavirin. Patients who had an extended rapid virologic response (undetectable HCV RNA levels at weeks 4 and 12) were randomly assigned after week 20 to receive the dual therapy for 4 more weeks (T12PR24) or 28 more weeks (T12PR48). Patients without an extended rapid virologic response were assigned to T12PR48.
Results : Of the 540 patients, a total of 352 (65%) had an extended rapid virologic response. The overall rate of sustained virologic response was 72%. Among the 322 patients with an extended rapid virologic response who were randomly assigned to a study group, 149 (92%) in the T12PR24 group and 140 (88%) in the T12PR48 group had a sustained virologic response (absolute difference, 4 percentage points; 95% confidence interval, -2 to 11), establishing noninferiority. Adverse events included rash (in 37% of patients, severe in 5%) and anemia (in 39%, severe in 6%). Discontinuation of all the study drugs was based on adverse events in 18% of patients overall, as well as in 1% of patients (all of whom were randomly assigned) in the T12PR24 group and 12% of the patients randomly assigned to the T12PR48 group (P<0.001).
Conclusions : In this study, among patients with chronic HCV infection who had not received treatment previously, a regimen of peginterferon-ribavirin for 24 weeks, with telaprevir for the first 12 weeks, was noninferior to the same regimen for 48 weeks in patients with undetectable HCV RNA at weeks 4 and 12, with an extended rapid virologic response achieved in nearly two thirds of patients. (Funded by Vertex Pharmaceuticals and Tibotec; ILLUMINATE ClinicalTrials.gov number, NCT00758043.)

@article{1906685,
abstract = {Background : Patients with chronic infection with hepatitis C virus (HCV) genotype 1 often need 48 weeks of peginterferon-ribavirin treatment for a sustained virologic response. We designed a noninferiority trial (noninferiority margin, -10.5\%) to compare rates of sustained virologic response among patients receiving two treatment durations.
Methods : We enrolled patients with chronic infection with HCV genotype 1 who had not previously received treatment. All patients received telaprevir at a dose of 750 mg every 8 hours, peginterferon alfa-2a at a dose of 180 mu g per week, and ribavirin at a dose of 1000 to 1200 mg per day, for 12 weeks (T12PR12), followed by peginterferon-ribavirin. Patients who had an extended rapid virologic response (undetectable HCV RNA levels at weeks 4 and 12) were randomly assigned after week 20 to receive the dual therapy for 4 more weeks (T12PR24) or 28 more weeks (T12PR48). Patients without an extended rapid virologic response were assigned to T12PR48.
Results : Of the 540 patients, a total of 352 (65\%) had an extended rapid virologic response. The overall rate of sustained virologic response was 72\%. Among the 322 patients with an extended rapid virologic response who were randomly assigned to a study group, 149 (92\%) in the T12PR24 group and 140 (88\%) in the T12PR48 group had a sustained virologic response (absolute difference, 4 percentage points; 95\% confidence interval, -2 to 11), establishing noninferiority. Adverse events included rash (in 37\% of patients, severe in 5\%) and anemia (in 39\%, severe in 6\%). Discontinuation of all the study drugs was based on adverse events in 18\% of patients overall, as well as in 1\% of patients (all of whom were randomly assigned) in the T12PR24 group and 12\% of the patients randomly assigned to the T12PR48 group (P{\textlangle}0.001).
Conclusions : In this study, among patients with chronic HCV infection who had not received treatment previously, a regimen of peginterferon-ribavirin for 24 weeks, with telaprevir for the first 12 weeks, was noninferior to the same regimen for 48 weeks in patients with undetectable HCV RNA at weeks 4 and 12, with an extended rapid virologic response achieved in nearly two thirds of patients. (Funded by Vertex Pharmaceuticals and Tibotec; ILLUMINATE ClinicalTrials.gov number, NCT00758043.)},
author = {Sherman, Kenneth E and Flamm, Steven L and Afdhal, Nezam H and Nelson, David R and Sulkowski, Mark S and Everson, Gregory T and Fried, Michael W and Adler, Michael and Reesink, Hendrik W and Martin, Marie and Sankoh, Abdul J and Adda, Nathalie and Kauffman, Robert S and George, Shelley and Wright, Christopher I and Poordad, Fred and ILLUMINATE Study Team, the and Van Vlierberghe, Hans},
issn = {0028-4793},
journal = {NEW ENGLAND JOURNAL OF MEDICINE},
keyword = {GENOTYPE-1,PLUS RIBAVIRIN,PEGINTERFERON ALPHA-2A},
language = {eng},
number = {11},
pages = {1014--1024},
title = {Response-guided telaprevir combination treatment for hepatitis C virus infection},
url = {http://dx.doi.org/10.1056/NEJMoa1014463},
volume = {365},
year = {2011},
}